Stannane, tributyl(1-ethoxyethenyl)- → 3'-Cyano-4'-fluoroacetophenone

HRID 2038375Notes

Reaction equation

HRID 2038375 reaction equation
C1(C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C(=CC=CC=2)C=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:48]1[CH:49]=[C:50]([C:55]#[N:56])[C:51]([F:54])=[CH:52][CH:53]=1.[CH2:57]([O:59]C([Sn](CCCC)(CCCC)CCCC)=C)[CH3:58]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:57]([C:48]1[CH:49]=[C:50]([C:55]#[N:56])[C:51]([F:54])=[CH:52][CH:53]=1)(=[O:59])[CH3:58]

Participants

6

Reactant 3

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 634876Binap, (A+-)-HCID 27249005-Bromo-2-fluorobenzonitrile

Product 1

HCID 224583893'-Cyano-4'-fluoroacetophenone

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Under an argon atmosphere, 449 mg (0.490 mmol) of tris(dibenzylideneacetone)dipalladium and 671 mg (1.078 mmol) of rac-1,1′-binaphthalene-2,2′diylbis(diphenylphosphane) are added to 4.90 g (24.5 mmol) of 3-bromo-6-fluorobenzenecarbonitrile in 180 ml of toluene. After the addition of 10.6 g (29.4 mmol) of (1-ethoxyvinyl)tributylstannane, the mixture is stirred under reflux overnight. The reaction mixture is subsequently concentrated and the residue is taken up in 200 ml of THF. After the addition of an aqueous 2N hydrogen chloride solution (50 ml), the mixture is stirred at room temperature for 4 h. The reaction mixture is subsequently neutralized using a saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product is purified by flash chromatography (mobile phase: cyclohexane/ethyl acetate 10:1→3:1). 3.50 g (88% of theory) of the title compound are obtained.

Workup

  1. temperatureunder reflux overnight
  2. concentrationThe reaction mixture is subsequently concentrated
  3. additionAfter the addition of an aqueous 2N hydrogen chloride solution (50 ml)
  4. stirringthe mixture is stirred at room temperature for 4 h
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic phases are dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product is purified by flash chromatography (mobile phase: cyclohexane/ethyl acetate 10:1→3:1)

Sources & evidence

ORD record
ord-069a62b88a0e4819891e3d6f6adf66e7
Source dataset
uspto-grants-2013_11
Patent number
US08575357B2

Reaction notes

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